Cervical cancer remains one of the leading causes of cancer among women, yet it is an entirely preventable disease. While HPV vaccination holds the greatest promise for reducing the global burden of cervical cancer, measurable reductions will not be realized for at least another 20 years. The only option for reducing cervical cancer incidence in the near term is increased accessibility of effective screening programs in regions with the highest burden of disease. The overarching goal of the Iquitos Screen-and-Treat Implementation Study (ISaTIS) is to move a strong evidence base for the use of screen-and-treat screening strategies into sustainable cervical cancer prevention programs appropriate for the health care context in the Loreto region of Peru and other middle income countries. Pilot participatory action research with key community stakeholders identified two acceptable alternative screening strategies for implementation evaluation: (1) single visit VIA- based screen-and-treat approach and (2) HPV DNA-based screening using self- or clinician-collected samples and HPV E6 oncoprotein triage-to-treatment. We will use a Participatory Action Research (PAR) approach, applying mixed methods, in an interrupted time series (ITS) design to develop, monitor, evaluate, and compare the two implementation strategies against current VIA-based standard of care screening. In Aim 1 we will conduct a community census in three communities in the Loreto region of Peru to establish cervical cancer screening registries and identify key members for working groups to facilitate our PAR approach. In Aim 2, we will use a series of focus group discussions, key informant interviews, and surveys to develop screening intervention monitoring and evaluation (M&E) criteria, objectives, methods, and instruments to be used in ongoing M&E of the implementation of each screening program using PAR processes. Our implementation strategies will be guided by the five domains outlined in the consolidated framework for implementation research (CFIR). In Aim 3 we will use the ITS design in a RE-AIM and CFIR-guided outcomes framework to evaluate the comparative effectiveness of each strategy. Qualitative and quantitative M&E methods iteratively executed in both pre- and post-implementation phases will be embedded into the overall ITS design, allowing real-time adaptation of the programs for broader sustainability. In Aim 4, we will synthesize our experience in a formal cost-effectiveness evaluation to allow policy makers to make comprehensive comparisons of each program relative to current standard of care and provide key data for future adoption in similar middle income countries. Publication of the outcomes of each process phase of our implementation research study will ensure maximal adoption of feasible and acceptable cervical cancer screening programs across a broad range of settings.